tbuckley/cabot-search huggingface dataset:
Burnout among early-career medical oncologists: A single-institution experience.
Authors: Anmol Singh, Lianchun Xiao, Barbara Jane O'Brien, Christopher Flowers, Eduardo Bruera, Van K. Morris, Amishi Yogesh Shah
Journal: Journal of Clinical Oncology (2022)

11015 Background: Burnout is a psychological syndrome defined by the Maslach Burnout Inventory (MBI) as emotional exhaustion, depersonalization, and a low sense of personal accomplishment. Risk of job-related burnout for early-career medical oncologists can significantly impact career longevity and health outcomes for providers and patients alike. Because little is known about burnout specific to early-career academic oncologists, we sought to characterize the prevalence of burnout and associated factors among Assistant Professors at MD Anderson Cancer Center (MDACC). Methods: For this IRB-approved retrospective study, an electronic survey was developed for Assistant Professors in medical oncology at MDACC. Participants were all involved directly in patient care with at least some clinical effort. Our survey included nine questions validated in the MBI addressing equally the 3 aforementioned domains of burnout. An additional 31 questions were formulated to assess personal and professional factors that may contribute to burnout at our institution (clinical workload, research expectations, communication, COVID, and home-life). Each question was scored on a scale of 1 to 5, with higher scores correlating to higher levels of burnout. Descriptive statistics were used to describe the prevalence of burnout, and logistic regression analyses were performed to identify characteristics associated with burnout. Results: Among 70 (of 86 total) Assistant Professors who responded, mean duration on faculty was 3.1 years (standard deviation +/-1.8). Mean clinical effort was 67% (range, 19-95). Gender identifications were 44% female, 54% male, and 2% non-binary. 54% of respondents reported symptoms of burnout already, including 21% endorsing severe burnout. Severe burnout was more common for solid tumor providers than liquid tumor providers (55% vs 13%, p =.03). Using the MBI, severe emotional exhaustion (25%) was more prevalent (p &lt;.0001) than depersonalization (6%) or lack of personal accomplishment (17%). Sentiments of being “emotionally drained” (20%), fatigue to face another day on the job” (37%), and “becoming more callous” (30%) were especially concerning among early-career faculty. Emotional exhaustion was associated with a feeling of less autonomy over personal decision making (p =.03) and female gender (p =.04). Conclusions: Burnout exists with high prevalence among early-career medical oncologists in this single-institution analysis. Emotional exhaustion was the specific manifestation of burnout in this population. Further validation of these data nationwide is anticipated. Interventions focusing on reducing emotional exhaustion are under development to reduce medical oncology-specific burnout in an academic setting for faculty retention and for deliverance of optimal care to patients with cancer.
The evolving paradigm of extracellular vesicles in intercellular signaling and delivery of therapeutic RNAs
Authors: Kevin V. Morris, Kenneth W. Witwer
Journal: Molecular Therapy (2022)

Extracellular vesicles (EVs) are approximately 30- to 150-nM particles that are generated by cells and are thought to mediate the transfer of bioactive cargo. 1 Witwer K.W. Wolfram J. Extracellular vesicles versus synthetic nanoparticles for drug delivery. Nat. Rev. Mater. 2021; 6: 103-106https://doi.org/10.1038/s41578-020-00277-6 Crossref Scopus (98) Google Scholar Substantial evidence suggests that an under-appreciated role of EVs is the mediation of intercellular signaling via microRNAs (miRNAs). 1 Witwer K.W. Wolfram J. Extracellular vesicles versus synthetic nanoparticles for drug delivery. Nat. Rev. Mater. 2021; 6: 103-106https://doi.org/10.1038/s41578-020-00277-6 Crossref Scopus (98) Google Scholar ,2 Kojima R. Bojar D. Rizzi G. Hamri G.C. El-Baba M.D. Saxena P. Auslander S. Tan K.R. Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment. Nat. Commun. 2018; 9: 1305https://doi.org/10.1038/s41467-018-03733-8 Crossref PubMed Scopus (336) Google Scholar However, the concept that miRNAs packaged into EVs mediate intercellular signaling has recently been called into question by Albanese and Chen et al., 3 Albanese M. Chen Y.F.A. Huls C. Gartner K. Tagawa T. Mejias-Perez E. Keppler O.T. Gobel C. Zeidler R. Shein M. et al. MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells. PLoS Genet. 2021; 17: e1009951https://doi.org/10.1371/journal.pgen.1009951 Crossref PubMed Scopus (67) Google Scholar who report that miRNAs do not seem to be packaged appreciably into EVs and, furthermore, when they are, they have little to no effect on recipient cells. These observations call into question myriad publications over the last decade that suggested that EV-packaged miRNAs alter target cell function and play a role in disease development and even, for example, in reprogramming of cells toward an oncogenic phenotype. 2 Kojima R. Bojar D. Rizzi G. Hamri G.C. El-Baba M.D. Saxena P. Auslander S. Tan K.R. Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment. Nat. Commun. 2018; 9: 1305https://doi.org/10.1038/s41467-018-03733-8 Crossref PubMed Scopus (336) Google Scholar ,4 Ye Y. Zhang X. Xie F. Xu B. Xie P. Yang T. Shi Q. Zhang C.Y. Zhang Y. Chen J. et al. An engineered exosome for delivering sgRNA:Cas9 ribonucleoprotein complex and genome editing in recipient cells. Biomater. Sci. 2020; 8: 2966-2976https://doi.org/10.1039/d0bm00427h Crossref PubMed Scopus (65) Google Scholar
Antibacterial Sericin Cryogels Promote Hemostasis by Facilitating the Activation of Coagulation Pathway and Platelets (Adv. Healthcare Mater. 11/2022)
Authors: Yuanyuan Zhu, Huan Liu, Sumei Qin, Cheng Yang, Qiying Lv, Zheng Wang, Lin Wang
Journal: Advanced Healthcare Materials (2022)

Cryogels In article number 2102717 by Zheng Wang, Lin Wang, and co-workers, a bifunctional hemostatic antibacterial dressing sericin-methacryloyl/Ag cryogel (SMC@Ag) is developed by freeze polymerization of methacryloyl modified sericin and in-situ sericin reduction of silver ions. It can promote the activation of the contact coagulation pathway and enhance the adhesion of platelets during the coagulation process, resulting in the outstanding hemostasis performance.
Prevention of venous thromboembolism in ambulatory patients with active cancer: Results from ACT4CAT study.
Authors: Nikolaos Tsoukalas, Athina Christopoulou, Anna Koumarianou, Eleni Timotheadou, Ilias Athanasiadis, Georgios Samelis, Stavros Peroukidis, Amanda Psyrri, Nikolaos Kapodistrias, Achilleas Nikolakopoulos, Stamatina G Demiri, Charalampos Andreadis, Alexandros Bokas, Alexandros Ardavanis, Epaminondas Samantas, Dimitrios Mavroudis, Vasileios Barbounis, Athanasios Athanasiadis, Pavlos Papakotoulas, Ioannis Boukovinas
Journal: Journal of Clinical Oncology (2022)

e18677 Background: Venous ThromboEmbolism (VTE), might be a challenge with a lot of negative consequences for patients with active cancer. VTE affects ongoing anticancer treatment, worsening morbidity and mortality, increases economic burden and escalates psychological distress. Incidence of VTE in patients with cancer reported 20%. Current guidelines recommend pharmacologic prophylaxis in ambulatory cancer patients with Khorana score ≥2. Methods: ACT4CAT is a prospective observational phase IV study conducted by HeSMO Greece, aiming to record the clinical practice of VTE prophylaxis in active cancer patients. Ambulatory patients who received thromboprophylaxis enrolled after signing informed consent. Study was approved by bioethics committee. Results: 691 patients from 19 oncology departments received thromboprophylaxis in 1 st line 57.6%, 2nd line 14.8%, adjuvant 9.0% and neoadjuvant 7.5%. Age ≥65 found 55%, BMI≥30 17.5% and males 63%. Tumor types: gastrointestinal 45.4%, lung 25.8%, urological 11.6%, gynecological 6.0%, breast 4.2% and others 7.0%. High-Risk for Thrombosis Agents (HRTAs) received 87.2%, specifically: platinum agents (56.3%), antimetabolites (54.2%) and immunotherapy (12.1%). 54,5% of the anticancer agents had potential drug-drug interaction (DDI) with anticoagulation treatment. Thromboprophylaxis duration lasted 5.3±3.5 months. Main agents were: tinzaparin 89.6%, fondaparinux 6.0%, bemiparin 2.2%, enoxaparin 1.6%, apixaban 0.3% and rivaroxaban 0.3%. Intermediate thromboprophylaxis dose received 68% of patients, lower in adjuvant setting (45.2%), with a preference in metastatic cases (OR: 1.5 95% CI: 1.02-2.3, p = 0.026). 14 thrombotic events reported (efficacy: 98.0%, 95%CI: 96.6-98.8%) and 12 grade 1 bleeding (1.7%, 95%CI: 1.0-3.0%). Conclusions: Prevention of VTE in ambulatory patients with active cancer found effective and safe. Apart from the Khorana score, specific patient characteristics, metastasis, HRTAs and DDIs seemed that affect clinical decision for thromboprophylaxis mainly with LMWHs and often on intermediate dose regardless the clinical setting. Oncologists appeared informed that CAT is not negligible risk. Clinical trial information: NCT03909399. [Table: see text]
Demographic and laboratory determinants of humoral immune responses and impact of different anti-SARS-CoV-2 vaccine platforms in patients with cancer: A systematic review and meta-analysis.
Authors: Diogo Martins-Branco, Angela Loizidou, Guilherme Nader Marta, Ana Tecic Vuger, Veronique Debien, Lieveke Ameye, Mariana Brandão, Kevin Punie, Chloe Spilleboudt, Karen Willard-Gallo, Ahmad Awada, Martine J. Piccart-Gebhart, Evandro de Azambuja
Journal: Journal of Clinical Oncology (2022)

1543 Background: Patients (pts) with cancer have increased mortality from COVID-19 and their vaccination is crucial to prevent severe infection. We aimed to identify demographic and laboratory determinants of humoral immune responses to COVID-19 vaccination in pts with cancer and investigate differences in responses based on the vaccine platform. Methods: We searched for records in PubMed, Embase, and CENTRAL up to 28/09/21, as well as conference proceedings from ASCO and ESMO 2021. We included studies of pts ≥16 yr with a cancer diagnosis, who were vaccinated against SARS-CoV-2. Studies were excluded if ≥10% of the participants had other causes of immunosuppression or baseline anti-SARS-CoV-2 spike protein antibodies (Ab)/previous COVID-19 (PROSPERO ID: CRD42021282338). For this subgroup analysis of studies that reported a proportion of pts with cancer and positive Ab titers at any timepoint following complete vaccination, a random-effects model was used to estimate the humoral response rate (HRR) with 95% confidence intervals (CI). Results: We included 64 records, reporting data from 10,511 cancer pts. The HRR in the overall population and by subgroup are shown in Table. Elder patients with hematologic cancers (59%, CI 47-70%, N = 667) and patients with lymphopenia (50%, CI 25-75%, N = 111) or hypogammaglobulinemia (36%, CI 19-57%, N=226) were the subgroups with lower HRR. Male (77%, CI 69-84%, N = 2,659) and Asian (84%, CI 54-96%, N = 37) pts showed a trend to lower HRR when compared with females and other races, respectively. Pts vaccinated with mRNA vaccine platforms (79%, CI 74-83%, N = 9,404) had numerically higher HRR than those receiving the adenovirus vaccines (28%, CI 19-40%, N = 74). Conclusions: This study highlights demographic and laboratory determinants of weaker immune responses to SARS-CoV-2 vaccination, permitting better identification of more vulnerable pts. Despite the small number of pts included receiving adenovirus vaccines, these data also suggest prioritizing mRNA platform vaccination in pts with cancer. [Table: see text]
HGG-61.Landscape of cancer predisposition in pediatric high-grade glioma
Authors: Mirjam Blattner-Johnson, Dominik Sturm, Philipp Sievers, Barbara Jones, Kathrin Schramm, Gnana Prakash Balasubramanian, Martin Sill, Natalie Jäger, Cornelis M van Tilburg, Till Milde, Kristian W Pajtler, Nicola Dikow, Steffen Hirsch, Christian Sutter, Felix Sahm, Olaf Witt, Stefan M Pfister, David T W Jones
Journal: Neuro-Oncology (2022)

Abstract Current estimates indicate that approximately 8–10% of cancer incidence in young patients can be attributed to constitutional alterations in genes linked to tumor initiation. The rarity and highly heterogeneous nature of high-grade glioma (HGG) in children and adolescents requires coordinated efforts to capture the diversity of subtypes in a normal-tumor matched sequencing cohort. Combining sequencing data of two registries based at the Hopp Children's Cancer Center (KiTZ) Heidelberg (INFORM and MNP2.0) allowed us to investigate the landscape of constitutional alterations across 350 children with high-grade gliomas. Both cohorts independently showed a surprisingly high proportion of patients (17%) with constitutional pathogenic alteration variants in cancer predisposition genes (n=40/233 and 23/128). Our results confirm a high frequency of alterations affecting genes of the DNA mismatch repair (MMR) pathway in 44% of IDH-mutant tumors (n=12/27). Additionally, we observed an almost exclusive correlation of MSH6 constitutional variation and somatic mutation in the IDH1 gene (n=7/8). A hypermutator phenotype defined by a tumor mutational burden &amp;gt;10 mutations/mb) was linked in 14/17 patients to a constitutional alteration in one of the following MMR genes: MLH1, MSH2, MSH6 or PMS2, with IDH-wildtype cases mostly classified as ‘RTK1 subtype’ by DNA methylation analysis. Constitutional alterations in TP53 were found in 5% of the total cohort. Furthermore, these tumors occurred exclusively in the group of H3-/IDH-wildtype glioblastoma (12%), and 8/18 tumors belong to the pedHGG_MYCN subgroup (conversely, this represents 40% of all ‘MYCN subtype’ patients, a highly significant enrichment over other subtypes (p&amp;lt;0.001). The overall high percentage of constitutional alterations in pediatric HGG warrants human genetics counselling for all affected patients and their families. Additionally, the strong correlation of MSH6 and IDH mutations as well as Li-Fraumeni-Syndrome and MYCN positive signature should be further explored as this might open the avenue for much needed new therapeutic approaches.
Impact of Silva classification system on the survival of HPV-related cervical adenocarcinoma patients with stage I ̃ IIIc1p.
Authors: Jiehui Li, Fenghu Li, Mu Junyu, Ran Li, Fan Mei, Lili Hu, Yanjun Du, Xue Tian, Hong Wei, Feiyue Yang, Mao Wanli, Qin Yao, Li Meng, Yin Shuishui
Journal: Journal of Clinical Oncology (2022)

e17505 Background: The incidence of cervical adenocarcinoma is increasing progressively in recent years and shows a younger trend that seriously threatens human health. However, the conventional pathological type of cervical adenocarcinoma is insufficient to predict the prognosis and therapeutic effect. Recently,the Silva classification system, a new pathological classification system was introduced and considered to have a better potential impact on the survival of HPV-related cervical adenocarcinoma patients. Methods: The clinical data of 102 patients with cervical adenocarcinoma from January 2010 to September 2021 were retrospectively included. All patients underwent radical resection of cervical cancer and were diagnosed as cervical adenocarci.noma by pathology.The HE staining sections of the patients were divided into SilvaA, SilvaB, and SilvaC types according to the Silva typing system. SPSS26.0 software was used for statistical analysis, Kaplan-Meier calculation was used for single-factor analysis, and COX stepwise regression model was used for multi-factor analysis. Results: Of the 102 patients with cervical adenocarcinoma who could be graded according to the Silva system, 14 (13.7%, 14/102) were SilvaA, 23 (22.5%, 23/102) SilvaB, and 65 (63.8%, 65/102) SilvaC. SilvaA type cervical adenocarcinoma patients were all stage I (IB1-IB3), no lymphatic or vascular invasion, and all patients were in a survival state by the end of follow-up. All patients with SilvaB cervical adenocarcinoma were stage I (IA2-IB3), without lymphatic or vascular invasion. Among 23 patients with Silva B, 2 patients died due to tumor, and the 5-year PFS and OS were 91.3%. Sixty-five patients with SilvaC type cervical adenocarcinoma (IB1-IIIC1P) and 15 patients died of tumor-related causes. FIGO stage, tumor size, lymph node invasion, and paralegal invasion were the influencing factors for survival and prognosis of SilvaC patients (P &lt;0.05). Conclusions: In the Silva typing system, SilvaC type has the worst prognosis, SilvaA type and SilvaB type are both stages I, without lymph node invasion, and the prognosis is better. Patients with SilvaC type are at the Ib1-IIIC1P stage and may have a lymphatic and vascular invasion. Late FIGO stage, lymph node metastasis, and paralegal infiltration are the influencing factors for survival and prognosis of SilvaC type.
Macular Degeneration and CETP Inhibition
Authors: Alan R. Tall, Daniel J. Rader, John J. P. Kastelein
Journal: JAMA Cardiology (2022)

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Upregulation of cellular retinoic acid-binding protein 2 enhances saturated fatty acid-accelerated prostate cancer progression
Authors: H. Sato, N. Shintaro, T. Yoshiko, I. Masanori, K. Soki, Y. Ryohei, K. Atsushi, N. Taketoshi, M. Huang, N. Kazuyuki, S. Mitsuru, Y. Toshiaki, H. Tomonori
Journal: European Urology (2022)
Apatinib plus etoposide as second-or higher-line treatment in recurrent or metastatic triple-negative breast cancer: A single-arm, open label, prospective, phase II clinical trial.
Authors: Mengru Cao, Hailing Lu, Shi Yan, Hui Pang, Lichun Sun, Chunhong Li, Xuesong Chen, Wei Liu, Jing Hu, Jian Huang, Ying Xing, Yingqi Chen, Ting He, Danni Zhao, Yuanyuan Sun, Lin Zhao, Xiaomeng Liu, Ningzhi Zhang, Li Cai
Journal: Journal of Clinical Oncology (2022)

e13069 Background: Due to the lack of targeted therapies, the standard of care for advanced triple-negative breast cancer (TNBC) was still chemotherapy, yet its effectiveness remains unsatisfied. Therefore, an urgent need exists to find a novel treatment option for patients with TNBC. The effect and safety profile of apatinib and etoposide have been demonstrated in several clinical trials for the treatment of late-stage TNBC respectively. In the present study, we aimed to investigate the potential effect of combination therapy of apatinib plus etoposide in recurrent or metastatic TNBC. Methods: Patients with late-stage TNBC who failed at least one line of chemotherapy were recruited in our study. Eligible patients were treated with in a 3-week cycle until disease progression or unacceptable toxicity for up to a maximum of 6 cycles. Apatinib could be declined to 250mg according to patients’ condition. Patients who completed their treatment were followed every 8 weeks and their disease progress was assessed scans according to RECIST 1.1. The primary endpoint was progress-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Safety was also evaluated. Results: From August 2018 to September 2021 a total of 40 patients were enrolled in this study. Their median age was 56-year old (range, 27-76) and had received a median of 3 (range, 2-6) previous lines chemotherapy. Until January 2022, among all eligible patients, 30 PFS events were observed. The median PFS was 6 months (95% CI, 3.77̃8.23) and the median OS was 24.53 months (95% CI, 10.23-38.83). Meanwhile, 4 patients achieved partial response, 21 patients achieved stable disease, the ORR was 10% and the DCR was 62.5% In addition, the most common adverse events were hypertension (65%), nausea (47.5%), vomiting (42.5%), and hand–foot syndrome (32.5%). The most common grade ≥ 3 adverse events were hypertension (5%) and proteinuria (5%). Conclusions: The results of the study exhibited a promising clinical effect of the combination therapy of apatinib plus etoposide and acceptable toxicity in recurrent or metastatic TNBC as second-or higher-line treatment. And more results will be updated with the progress of this clinical trial. Clinical trial information: ChiCTR1800018497.